DK157296B - 2-CHLORO-PYRIDE COMPOUNDS FOR USE AS BASIC MATERIALS IN THE PREPARATION OF HERBICIDE PYRIDE COMPOUNDS - Google Patents

Description

DK 157296 B

The present invention relates to novel 2-chloro-pyridine compounds for use as a starting material in the preparation of herbicidal pyridine compounds of the general formula 5 wherein XX is hydrogen or a chlorine atom,

R1 is hydrogen or an alkyl radical of 1-4 carbon atoms; and R 2 is a cyano group, a carboxyl group, a carboxamido group -CNR 3 R 4 wherein R 3 is hydrogen or an alkyl radical and R 4 is 15 "hydrogen, an optionally hydroxy or phenyl substituted alkyl radical of 1-4 carbon atoms, a phenyl or chlorophenyl radical, an alkoxy radical of 1-4 carbon atoms or a group -Nr5r6 wherein R5 is hydrogen or alkyl of 1-4 carbon atoms, 20 and R® is hydrogen, alkyl of 1-4 carbon atoms, phenyl or chlorophenyl, or the group -NR3R4 forms a pyrrolidino , piperidino or morpholine radical; a group -CSR7 wherein R7 is

II

0 alkyl or phenyl; an alkoxycarbonyl group in which the alkoxy group may be straight or branched, optionally carrying one or more hydroxy, alkoxy or halogen substituents, or carrying a substituent of formula (I) wherein R 2 is a

-C-O-radical; a group -C (OCH2CH2) n ° R8 where R8 is an alkyl-II II

0 0 30 radicals having 1-4 carbon atoms and n is an integer from 1 to 5 inclusive; a cyclohexyloxycarbonyl radical optionally substituted by one or more halogen atoms or methyl radicals; an alkenyloxycarbonyl radical wherein the alkenyl group contains from 3 to 6 carbon atoms; a phenoxycarbonyl radical optionally carrying one or more halogen or methyl substituents; or a benzyl oxycarbonyl radical whose phenyl group optionally carries one or more halogen or methyl substituents; and in the case of compounds wherein R 2 is a carboxyl group, salts thereof.

DK 157296B

2

The compounds of the invention are peculiar in that they have the formula -χχ where Y is hydrogen or chlorine.

The compounds of formula I have an unexpectedly stronger herbicidal activity than similar compounds with a chlorine atom instead of the CF 3 group at the 5-position of the pyridine ring.

The compounds of the invention are converted to the corresponding novel 5-trifluoro compounds by reaction with a fluorinating agent, e.g. antimony trifluoride or liquid fluorine hydrogen to provide the starting materials II '.

20

Method A is outlined by the following scheme: 25 30 35

DK 157296 B

3

Procedure A

Y PCÎI3 • '"OC 0

ABOUT

10

-W

Vo3 - h3 (III)

Demethylating agent F.jC Y

20 (HD £ ek ek5 · 9yridine -A γΥ

hydrochloride OH

(IV) 25 1 | 9 Base (IV) + Hal-CH-κ - ^ (I).

In process A, the symbols R1, r2 and γ have the meaning previously assigned to them, Hal is a halogen, preferably chlorine or bromine, and M is a cation, e.g. sodium.

In process A, the halogen pyridine 11 'is reacted with a metal salt of p-methoxyphenol, e.g. the sodium salt of p-methoxyphenol. The reaction is preferably carried out in a solvent or diluent, e.g. methyl ethyl ketone, tetrahydrofuran, dimethyl sulfoxide or dimethyl acetamide. The 2-p-methoxy-phenoxy compound (III) thus obtained

DK 157296 B

4 is then thylated in a standard manner, e.g. by heating with pyridine hydrochloride or with hydrogen bromide in acetic acid to give the corresponding p-hydroxy compound (IV). This is then in the form of its metal salt (e.g., the sodium or potassium salt) reacted with the desired haloalkanoic acid derivative (V) to form the desired compound I. Preferably, this reaction is carried out in a solvent or diluent, e.g. methylethy1keton.

Procedure B is outlined in the following scheme: <ΓΙ + HO-0HH - Βί3β> (IV) R1 (IV) +. Hal-CH-R2 - (I) According to Method B, the 2-halo pyridine (II ") is reacted with hydroquinone in the presence of a base to form the p-hydroxyphenoxy compound (IV) already disclosed in process A. The reaction is preferably carried out in a solvent or diluent for the reactants Examples of suitable solvents include aprotic solvents, for example, dimethylformamide. The base used for the reaction may be, for example, an inorganic base, for example, sodium or potassium carbonate.

The second step of method B is identical to the last step of method A and requires no further description.

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DK 157296 B

5

Procedure C

5 (II.) + HO-QCH.-R2 BaS ^ W

(VI) According to Method C, the 2-halo pyridine (II1) is reacted with a 2- (p-hydroxyphenoxy) propionic acid derivative VI in the presence of a base to give the compound I directly. The derivatives VI are known per se, or can be prepared in conventional ways. The reaction is preferably carried out in the vicinity of a solvent or diluent for the reaction participants. Examples of solvents include lower ketones, e.g. methyl ethyl ketone. The reaction may be accelerated by heating, and may e.g. conveniently carried out at the solvent reflux temperature of the solvent. Examples of bases 20 for use in the reaction include inorganic bases, e.g. anhydrous potassium carbonate.

The starting materials II according to the invention can themselves be produced in various ways. Thus, 2-chloro-5-trichloromethylpyridine, e.g. is obtained by reaction of 3-methylpyridine with chlorine in liquid phase under the influence of ultraviolet light. The reaction of 3-methylpyridine (as free base or in the form of a chlorine) with chlorine is generally carried out in an inert organic solvent. Conveniently, the solvent is a halogenated hydrocarbon, e.g. tetrachlorocarbon, with other solvents can be used, e.g. hydrocarbons or ethers, provided they do not react under the conditions used to form unacceptable amounts of undesired by-products. The reaction is slow at or below room temperature and is therefore accelerated by heat. Suitable reaction temperatures are e.g. in the range 50 to 130 ° C. The solution can be heated under reflux. It is preferable to use terrain reactants and solvents. Ultraviolet light can

DK 157296 B

6, the reaction is fed from a suitable electric lamp, so that for the highest efficiency it can be immersed in the reaction mixture. The reaction generally provides a mixture of products from which the individual 2-chloro-5-trichloromethylpyridine 5 can be isolated in conventional ways, e.g. at destination.

Preparation of the Compounds of the Invention

Preparation of 2-chloro-5-trichloromethylpyridine 10 A. 55 g of 2-bromo-5-methylpyridine in ter tetrachlorocarbon (600 ml) was filtered and then treated with ter chlorine hydrogen to give the hydrochloride. The solid that separated was broken up and the mixture heated to reflux. Ter chlorine was passed through the boiling mixture for 6½ hours under irradiation with an ultraviolet lamp placed inside the reaction flask. The mixture was then cooled, filtered and evaporated to a pale yellow liquid which solidified upon cooling. This was identified as the downstream chlorine compound by its nuclear magnetic resonance spectrum.

B. 10 ml of 3-methylpyridine was dissolved in 300 ml of tetrachlorocarbon. The solution was heated to reflux (approx. 80 ° C) and ter chlorine gas was passed through the boiling mixture for 3 hours, while being irradiated internally from a 100 watt ultraviolet lamp which gave light with a bell length of 185 nm. Preparative thin layer chromatography (s i-lica, chloroform / cyclohexane) on an evaporated preve of the solution afforded three main products in a total yield of 10% 15%. The most abundant of these was identified by its nuclear magnetic resonance spectrum as the single 2-chloro-5-trichloromethylpyridine. This was confirmed by mass spectrographic analysis of the resulting reading. The other two major products were 2-chloro-3-trichloromethylpyridine and a 35 di (trichloromethyl) pyridine, which was present in an amount of about

half and approx. one-tenth of the main product.

f 4

DK 157296 B

7 C. 15 g of 3-methylpyridine in 200 ml of tetrachlorocarbon was treated with ter HCl gas to give the hydrochloride. The resulting oily mixture was stirred and heated to reflux. Chlorine gas was bubbled into the 4-hour reflux mixture for 4 hours, while the interior was illuminated with an ultraviolet lamp used in A above. The reaction mixture was then cooled and separated by decantation in solution and oily solid. The latter was purified and shown to contain unreacted 3-methyl-10-pyridine salt. The former was evaporated to an oily semi-solid which, by thin-layer chromatography, was shown to have the properties of 2-ehloro-5-trichloromethylpyridine.

Preparation of 2,3-dichloro-5-trichloromethylpyridine 108 g of 2-amino-5-methylpyridine in 300 ml of glacial acetic acid was heated to 90-100 ° C, while 160 g of bromine in 55 ml of acetic acid was slowly added with stirring. After the addition was complete, the mixture was stirred and heated for an additional 30 minutes and then allowed to cool overnight. The solid which separated was filtered and mixed with ice, and the mixture was neutralized with concentrated ammonia, keeping the temperature at 0 to 5 ° C. The solid was collected, washed with water and dried to give 2-amino-3-bromo-5-methylpyridine.

145 g of this product was dissolved in 750 ml of concentrated hydrochloric acid and 450 ml of water and the solution was cooled to -10 ° C. 54 g of sodium nitrite in 450 ml of cold water were added dropwise under stirring for 90 minutes while maintaining the mixture at -5 ° C. The solution was stirred for an additional 2 hours and then basified with concentrated ammonia, keeping the temperature below 20 ° C. The solid which separated was washed with water terre. dissolved in ether (1500 ml) and washed with 35 cold sodium hydroxide solution (IM, 1 L). The ether solution was washed twice with water (1 liter portions), dried and evaporated to give 3-bromo-2-chloro-5-methylpyridine.

8

DK 157296 B

54 g of this product in 650 ml of tetrachlorocarbon were treated with ter chlorine hydrogen. The precipitate was broken up and the suspension pension heated under reflux while ter chlorine was bubbled into the mixture under irradiation from an ultraviolet light source. After 4½ hours, the mixture was cooled, filtered and the filtrate evaporated to give 2,3dichloro-5-trichloromethylpyridine. The mass spectrum was consistent with the structure attached to this compound.

Preparation of the intermediate products II '

Preparation of 2-chloro-5-trifluoromethylpyridine A. 18 g of 2-chloro-5-trichloromethylpyridine and 50 g of antimony trifluoride were heated together at 140-145 ° C for 1 hour. The mixture was cooled, mixed with ice and concentrated hydrochloric acid and extracted with ether. The extracts were washed with water, triturated with magnesium sulfate and evaporated. The products of several such preparations were combined and distilled at atmospheric pressure through a short sail packed with

Fenske rings. The product boiling at 124-154 ° C was collected and identified as 2-chloro-5-trifluoromethylpyridine.

B. 30.8 g of 2-chloro-5-trichloromethylpyridine and 80 g of anhydrous hydrogen fluoride were heated to 200 ° C for 10 hours with stirring in an autoclave. The mixture was cooled, poured on ice and neutralized at 0 ° C. The mixture was filtered and the residue and filtrate extracted with ether. The ether extracts were washed with water, dried and evaporated to give an oil. This was distilled and the fraction boiling at 140-154 ° C was collected. Analysis showed that it consisted of 2-chloro-5-trifluoromethylpyridine together with some 2-fluoro-5-trifluoromethylpyridine.

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DK 157296 B

9

Preparation of 2,3-cichloro-5-trifluoromethylpyridine A. 1.0 g of 2,3-dichloro-5-trichloromethylpyridine and 3.0 g of antimony trifluoride were heated together to 170-180 ° C for 30 minutes. The mixture was then cooled, mixed with ice and water and extracted with ether. The ether extracts gave a brown oil containing a mixture of 2,3-dichloro-5-trifluoromethylpyridine and 3-chloro-2-fluoro-5-trifluoromethylpyridine together with a minor amount of 2,3-dichloro-3-chlorodifluoromethylpyridine.

B. 35 g of 2,3-dichloro-5-trichloromethylpyridine was heated with 100 g of anhydrous hydrogen fluoride in an autoclave to 200 ° C for 10 hours with stirring. The cooled reaction mixture was poured on ice and neutralized with sodium hydroxide at 0 ° C.

The mixture was extracted with 750 ml of methylene chloride. The extracts were washed with water (500 ml), sodium carbonate solution (500 ml) and water (500 ml) dried and evaporated.

The residual oil was distilled and the fraction of boiling point 77 to 83eC / 25 torr was collected and identified as 2,3-dichloro-5-trifluoromethylpyridine.

C. 61 g of antimony trifluoride was melted in vacuo to remove moisture. The cooled material was broken up and heated to 65-70 ° C, while 6.6 g of antimony pentachloride was added 25 dropwise with stirring. 40 g of 2,3-dichloro-5-trichloromethylpyridine was then added dropwise to the mixture and the whole was heated to 160 ° C over 45 minutes. The mixture was cooled and steam distilled. The oil, which was distilled off, was extracted with ether (2 x 100 ml).

The ether extract was washed with tartaric acid solution, then water, sodium bicarbonate and water and dried. The remaining oil was distilled off. The fraction boiling at 71 to 80 ° C / 18 torr was identified as 2,3-dichloro-5-trifluoromethylpyridine.

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Claims (1)

R 1 is hydrogen or an alkyl radical of 1-4 carbon atoms; and R 2 is a cyano group, a carboxyl group, a carboxamido group -CNR 3 R 4 wherein R 3 is hydrogen or an alkyl radical and R 4 is 10 hydrogen, an optionally hydroxy or phenyl substituted alkyl radical of 1-4 carbon atoms, a phenyl or chlorophenyl radical, an alkoxy radical of 1-4 carbon atoms or a group -NR5R® wherein R5 is hydrogen or alkyl of 1-4 carbon atoms and R6 is hydrogen, alkyl of 1-4 carbon atoms, phenyl or chlorophenyl, or the group -NR3R4 a pyrrolidino, pyridino or morpholine radical; a group -CSR?, wherein R? is II alkyl or phenyl; an alkoxycarbonyl group in which the alkoxy group may be straight or branched and optionally carrying one or more hydroxy, alkoxy or halogen substituents, or carrying a substituent of formula (I) wherein R 2 is a -C-O radical; a group -C (OCH2CH2) NOR8 · wherein R8 is an alkyl-II IIO radical of 1-4 carbon atoms and n is an integer from 1 to 5 inclusive; a cyclohexyloxycarbonyl radical optionally substituted by one or more halogen atoms or methyl radicals; an alkenyloxycarbonyl radical wherein the alkenyl group contains from 3 to 6 carbon atoms; a phenoxycarbonyl radical optionally carrying one or more halogen or methyl substituents; or a benzyloxycerbonyl radical whose phenyl group optionally bears one or more halogen or methyl substituents; and where it turns. compounds of which R 2 is a carboxyl group, salts thereof, characterized in that they have the formula 10 wherein Y is hydrogen or chlorine. 15 20 25 30 35